MECHANISM OF CATECHOLAMINE SECRETION

儿茶酚胺的分泌机制

• 批准号: 3336737
• 负责人: ARUN R. WAKADE
• 金额: $ 16.2万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336737
• 关键词: adrenal medulla; adrenergic agents; adrenergic receptor; alpha antiadrenergic agent; anticholinergic agent; calcium channel; catecholamine inhibitor; catecholamines; cholinergic agents; chromaffin cells; cyclic AMP; cyclic GMP; denervation; enzyme inhibitors; exocytosis; forskolin; inositol phosphates; laboratory rat; membrane channels; muscarine; muscarinic receptor; neuronal transport; neuropeptides; neuropharmacology; nicotine; nicotinic receptors; norepinephrine; peripheral nervous system; protein kinase C; radiotracer; secretion; splanchnic nerves; sympathetic nervous system; synapses; tissue /cell culture

Chromaffin cells of the adrenal medulla continue to serve as a powerful tool to explore the field of neurohumoral secretion. In 1981 PI introduced a preparation to study catecholamine (CA) secretion from the isolated perfused adrenal gland of the rat. Using this preparation a number of physiological and pharmacological properties of secretion have been established. Most recently, several new observations have been made which made, which are of potential importance. The observations are as follows: 1) Secretion of CA is induced by nicotine as well as muscarine. Nicotine enhances influx of Ca45, whereas muscarine does not, although muscarine-evoked secretion is dependent on calcium. Nicotine-evoked secretion is desensitized within 20 min but muscarine-evoked is not up to 45 min. - a possibility of differential routes of mobilization of calcium and its utilization in exocytosis. 2) As long as 2 hr of continuous perfusion with 55 mM K-Krebs solution causes a pronounced secretion of CA, with only a modest degree of desensitization. Excess K-evoked secretion is totally dependent on calcium - a possibility of slow inactivation of calcium channels. 3) A marked secretion of CA obtained during perfusion with 55 mM K-Krebs solution is not associated with a reduction in the medullary CA content; however, after blockade of tyrosine hydroxylase there was a significant reduction in CA content - a possibility of reutilization of chromaffin storage vesicles. 4) Secretion of CA evoked by stimulation of splanchnic nerves at higher frequencies is more effectively reduced by cholinergic receptor antagonists than that evoked at lower frequencies - a possibility of another transmitter, in addition to acetylcholine, (ACh), released from splanchnic nerves to evoke secretion of CA. 5) Protein kinase C activator (phorbol esters) potentiate CA secretion and Ca45 uptake initiated by nicotine. Phorbol esters have no effect on muscarine-evoked secretion. cAMP activator (forskolin) potentiates CA secretion evoked by nicotine as well as muscarine - a possibility of intracellular messengers participating at different steps of exocytosis to evoke secretion. Biochemical, physiological and pharmacological experiments have been designed to discern each of the above possibilities in hope of extending our understanding of the secretory mechanism.

肾上腺髓质的染色体细胞继续用作 探索神经肿瘤分泌领域的强大工具。 在 1981 PI引入了研究儿茶酚胺（CA）的准备工作。 大鼠孤立的灌注肾上腺的分泌。 使用此准备多种生理和 分泌的药理特性已建立。 最近，已经进行了一些新的观察结果 制造，这很重要。 观察是 以下内容：1）Ca的分泌由尼古丁和 毒arine。 尼古丁可增强CA45的涌入，而毒arine 尽管毒arine诱发的分泌取决于 钙。 尼古丁诱发的分泌在20分钟内脱敏 但是，毒arine诱发的诱发时间最多不超过45分钟。 - 可能性 动员钙及其利用的差异途径 胞吞作用。 2）长达2小时的连续灌注，用55毫米 k-krebs解决方案导致CA的明显分泌，仅在 适度的脱敏程度。 多余的K诱发的分泌是 完全取决于钙 - 可能缓慢失活的可能性 钙通道。 3）在 用55毫米K-krebs溶液灌注与A 减少髓质Ca含量；但是，封锁后 酪氨酸羟化酶的Ca显着降低 内容 - 铬蛋白储存的可能性 囊泡。 4）通过刺激闪烁的CA的分泌 较高频率下的神经更有效地降低了 胆碱能受体拮抗剂比在较低的 频率 - 除了其他发射器的可能性 乙酰胆碱（ACH），从诊断神经释放到唤起 分泌 5）蛋白激酶C活化剂（佛波酯） 尼古丁发起的增强Ca分泌和CA45摄取。 佛波酯对毒arine诱发的分泌没有影响。 营地激活剂（福斯科林）增强了CA分泌 尼古丁和毒品 - 细胞内的可能性 参与胞吞作用的不同步骤的使者引起 分泌。 生化，生理和药理 实验旨在辨别上述每个 希望扩展我们对 分泌机制。